PROJECT SUMMARY This Administrative Supplement requests one year of funding to support unforeseen costs associated with the University of Kansas Alzheimer?s Disease Center (KU ADC) Mitochondrial Genomics and Metabolism (MGM) Core. MGM Core activities span a spectrum from fundamental mitochondrial biology research that addresses AD etiology and pathogenesis, to clinical trials that assess lifestyle and pharmacologic intervention impact. An unanticipated growth in the number of investigators requesting MGM Core support, and an emergent unforeseen need for the Core to develop new biomarker infrastructure, predicates this request. With respect to MGM biomarker-related activities, mitochondrial target engagement biomarkers newly developed and validated by the MGM Core in actual clinical studies spurred unanticipated clinical trial growth. This put further service demands on the Core, and generated opportunities to develop additional target engagement biomarkers. As an extension of this, we realize a need to extend our biomarker development efforts to cerebrospinal fluid (CSF). Accomplishing this requires critical infrastructure expansion. Also, partly due to our successes, increased NIA AD research pay lines, and technology advances the volume of service requests we currently receive exceeds what we planned for. To strategically address these unforeseen needs and capitalize on unanticipated opportunities, support through this Administrative Supplement will help us: (1) expand induced pluripotent stem cell (iPSC) infrastructure, as well as blood-based mitochondrial biomarker measurement and development throughput; (2) develop and provide CSF mitochondrial biomarker measurements; and (3) establish a biomarker dataset linked to clinical, genomic, and biospecimen data. We can achieve these aims in one year by supporting effort for a laboratory technician and a physician extender who performs lumbar punctures on Clinical Cohort participants. Funds to support other personnel pertinent to these efforts are also requested.